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Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells

Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO...

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Autores principales: Katawa, Gnatoulma, Layland, Laura E., Debrah, Alex Y., von Horn, Charlotte, Batsa, Linda, Kwarteng, Alexander, Arriens, Sandra, W. Taylor, David, Specht, Sabine, Hoerauf, Achim, Adjobimey, Tomabu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288720/
https://www.ncbi.nlm.nih.gov/pubmed/25569210
http://dx.doi.org/10.1371/journal.pntd.0003414
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author Katawa, Gnatoulma
Layland, Laura E.
Debrah, Alex Y.
von Horn, Charlotte
Batsa, Linda
Kwarteng, Alexander
Arriens, Sandra
W. Taylor, David
Specht, Sabine
Hoerauf, Achim
Adjobimey, Tomabu
author_facet Katawa, Gnatoulma
Layland, Laura E.
Debrah, Alex Y.
von Horn, Charlotte
Batsa, Linda
Kwarteng, Alexander
Arriens, Sandra
W. Taylor, David
Specht, Sabine
Hoerauf, Achim
Adjobimey, Tomabu
author_sort Katawa, Gnatoulma
collection PubMed
description Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO. Using flow cytometry, filarial-specific cytokine responses and PCR arrays, we compared the immune cell profiles, including Th subsets, in individuals presenting the two polar forms of infection and endemic normals (EN). In addition to elevated frequencies of memory CD4(+) T cells, individuals with HO showed accentuated Th17 and Th2 profiles but decreased CD4(+)CD25(hi)Foxp3(+) regulatory T cells. These profiles included increased IL-17A(+), IL-4(+), RORC2(+) and GATA3(+)CD4(+) T cell populations. Flow cytometry data was further confirmed using a PCR array since Th17-related genes (IL-17 family members, IL-6, IL-1β and IL-22) and Th2-related (IL-4, IL-13, STAT6) genes were all significantly up-regulated in HO individuals. In addition, stronger Onchocerca volvulus-specific Th2 responses, especially IL-13, were observed in vitro in hyperreactive individuals when compared to GEO or EN groups. This study provides initial evidence that elevated frequencies of Th17 and Th2 cells form part of the immune network instigating the development of severe onchocerciasis.
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spelling pubmed-42887202015-01-12 Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells Katawa, Gnatoulma Layland, Laura E. Debrah, Alex Y. von Horn, Charlotte Batsa, Linda Kwarteng, Alexander Arriens, Sandra W. Taylor, David Specht, Sabine Hoerauf, Achim Adjobimey, Tomabu PLoS Negl Trop Dis Research Article Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO. Using flow cytometry, filarial-specific cytokine responses and PCR arrays, we compared the immune cell profiles, including Th subsets, in individuals presenting the two polar forms of infection and endemic normals (EN). In addition to elevated frequencies of memory CD4(+) T cells, individuals with HO showed accentuated Th17 and Th2 profiles but decreased CD4(+)CD25(hi)Foxp3(+) regulatory T cells. These profiles included increased IL-17A(+), IL-4(+), RORC2(+) and GATA3(+)CD4(+) T cell populations. Flow cytometry data was further confirmed using a PCR array since Th17-related genes (IL-17 family members, IL-6, IL-1β and IL-22) and Th2-related (IL-4, IL-13, STAT6) genes were all significantly up-regulated in HO individuals. In addition, stronger Onchocerca volvulus-specific Th2 responses, especially IL-13, were observed in vitro in hyperreactive individuals when compared to GEO or EN groups. This study provides initial evidence that elevated frequencies of Th17 and Th2 cells form part of the immune network instigating the development of severe onchocerciasis. Public Library of Science 2015-01-08 /pmc/articles/PMC4288720/ /pubmed/25569210 http://dx.doi.org/10.1371/journal.pntd.0003414 Text en © 2015 Katawa et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Katawa, Gnatoulma
Layland, Laura E.
Debrah, Alex Y.
von Horn, Charlotte
Batsa, Linda
Kwarteng, Alexander
Arriens, Sandra
W. Taylor, David
Specht, Sabine
Hoerauf, Achim
Adjobimey, Tomabu
Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells
title Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells
title_full Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells
title_fullStr Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells
title_full_unstemmed Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells
title_short Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells
title_sort hyperreactive onchocerciasis is characterized by a combination of th17-th2 immune responses and reduced regulatory t cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288720/
https://www.ncbi.nlm.nih.gov/pubmed/25569210
http://dx.doi.org/10.1371/journal.pntd.0003414
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